Open research Africa最新文献

{"title":"Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in <i>Plasmodium berghei</i> ANKA.","authors":"Jean Chepngetich, Brenda Muriithi, Beatrice Gachie, Kevin Thiong'o, Mercy Jepkorir, Jeremiah Gathirwa, Francis Kimani, Peter Mwitari, Daniel Kiboi","doi":"10.12688/openresafrica.13436.1","DOIUrl":"10.12688/openresafrica.13436.1","url":null,"abstract":"<p><strong>Background: </strong>Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable <i>Plasmodium</i> kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant <i>Plasmodium berghei</i> parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kβ), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in <i>Plasmodium berghei</i> ANKA.</p><p><strong>Methods: </strong>We used <i>in silico</i> bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1. Using qPCR analysis, we measured the mRNA amount of PANK1, DAGK, and PI4Kβ at trophozoites and schizonts stages.</p><p><strong>Results: </strong>We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kβ possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His, while DAGK contained K270R and K292R mutations. PI4Kβ had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kβ in the trophozoites but upregulation at the schizonts stages in the AQr parasites.</p><p><strong>Conclusions: </strong>The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and their impact on drug responses require investigations using reverse genetics techniques in malaria parasites.</p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":" ","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49449280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in Plasmodium berghei ANKA","authors":"Jean Chepngetich, Brenda Muriithi, Beatrice Gachie, Kevin Thiong'o, Mercy Jepkorir, Jeremiah Gathirwa, Francis Kimani, Peter Mwitari, Daniel Kiboi","doi":"10.12688/openresafrica.13436.3","DOIUrl":"https://doi.org/10.12688/openresafrica.13436.3","url":null,"abstract":"<ns3:p>Background Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable <ns3:italic>Plasmodium</ns3:italic> kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant <ns3:italic>Plasmodium berghei</ns3:italic> parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kβ), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in <ns3:italic>Plasmodium berghei</ns3:italic> ANKA. Methods We used <ns3:italic>in silico</ns3:italic> bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1. Using qPCR analysis, we measured the mRNA amount of PANK1, DAGK, and PI4Kβ at trophozoites and schizonts stages. Results We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kβ possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His, while DAGK contained K270R and K292R mutations. PI4Kβ had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kβ in the trophozoites but upregulation at the schizonts stages in the AQr parasites. Conclusions The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and their impact on drug responses require investigations using reverse genetics techniques in malaria parasites.</ns3:p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135778689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cultivar-specific responses of tomato essential oils to tomato red spider mite (Tetranychus evansi): Implications for pest management","authors":"Lucy Kananu Murungi, Stephen Agong, Peter Masinde, Ahmed Hassanali, Markus Knapp","doi":"10.12688/openresafrica.14334.1","DOIUrl":"https://doi.org/10.12688/openresafrica.14334.1","url":null,"abstract":"<ns4:p><ns4:bold>Background: </ns4:bold>The tomato (<ns4:italic>Solanum lycopersicum</ns4:italic> L.) is a widely cultivated and nutritionally valuable plant species, known for its culinary and health benefits. However, tomato crops are susceptible to various pests, including the tomato red spider mite (<ns4:italic>Tetranychus evansi</ns4:italic>), which can cause substantial yield losses. Essential oils from plants have shown potential as natural alternatives for pest management.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>This study investigated the interaction between essential oils from seven different tomato accessions namely; 1 (money maker), 13 (marglobe), 51 (PI 134417), 162 (JKUAT 22/202183), 182 (JKUAT 19), 428 (LA 2185) and 460 (LO 3279) and <ns4:italic>T. evansi</ns4:italic>. The aim was to understand the role of essential oils in shaping mite behavior. Essential oils were extracted from these diverse tomato accessions using steam distillation. The response of spider mites to these essential oils was assessed using Y-tube olfactometer and glass slide bioassays. Gas chromatography/mass spectrometry was used to analyze the composition of volatile compounds released by the essential oils.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>Spider mite responses to different concentrations of essential oils were not significantly different among accessions. However, specific accessions, such as 51 and 428, elicited negative responses across concentrations. Analysis of volatile compounds revealed qualitative and quantitative variations in essential oil composition among accessions. Compounds like 2-tridecanone, 2-undecanone, β-caryophyllene, and α-humulene exhibited distinct abundance patterns across accessions.</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold>The study provides insights into the complex interaction between tomato essential oils and spider mite behavior. While concentrations of essential oils did not strongly influence mite responses, the unique composition of essential oils in different accessions played a crucial role. These findings suggest the potential for selective breeding of tomato varieties with specific essential oil profiles to enhance resistance to spider mites. The research contributes to our understanding of natural pest management strategies and underscores the importance of phytochemical diversity in shaping arthropod behavior.</ns4:p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135385191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Funding and COVID-19 research in Africa: two years on, are the research needs of Africa being met?","authors":"Emilia Antonio, Moses Alobo, Marta Tufet Bayona, Kevin Marsh, Proochista Ariana, Alice Norton","doi":"10.12688/openresafrica.14185.1","DOIUrl":"https://doi.org/10.12688/openresafrica.14185.1","url":null,"abstract":"<ns4:p>Background: The Coronavirus disease 2019 (COVID-19) pandemic caused significantly lower reported mortalities on the African continent as compared to other regions. Yet, many countries on the continent are still contending with the devastating economic, social and indirect health impacts. African researchers and policy makers have identified research priority areas which take cognisance of the unique research needs of African countries. A baseline assessment of the alignment of funded research in Africa to these priorities and World Health Organization’s COVID-19 research priorities was undertaken in July, 2020. We present a two-year update to this analysis of funded COVID-19 research in Africa.</ns4:p><ns4:p> Methods: Data captured in the UK Collaborative on Development Research and Global Research Collaboration for Infectious Disease Preparedness COVID-19 Research Project Tracker as of 15th July, 2022 was analysed. An additional analysis of institutions receiving funding for COVID-19 research is presented. We also analysed the change in funding for COVID-19 research in Africa since July, 2020.</ns4:p><ns4:p> Results: The limited COVID-19 research identified in Africa early in the pandemic has persisted over the subsequent two-year period assessed. When number of projects are considered, governmental funders based in Europe and United States supported the most research. Only nine research funders based in Africa were identified. A number of partnerships between African institutions and institutions based on other continents were identified, however, most research projects were undertaken in research institutions based in Africa only. Our findings highlight the relevance of the WHO research priorities for the pandemic response in Africa. Many research questions raised by African researchers remain unaddressed, among which are questions related to clinical management of COVID-19 infections in Africa.</ns4:p><ns4:p> Conclusions: Two years after the identification of Africa’s COVID-19 research priorities, the findings suggest a missed opportunity in new research funding to answer pertinent questions for the pandemic response in Africa.</ns4:p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135878762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lumefantrine pressure selects nonsynonymous mutation in cysteine desulfurase IscS gene in the rodent malaria parasite Plasmodium berghei ANKA","authors":"Beatrice Gachie, Jean Chepngetich, Brenda Muriithi, Kelvin Thiong’o, Jeremiah Gathirwa, Francis Kimani, Peter Mwitari, Gabriel Magoma, Daniel Kiboi","doi":"10.12688/openresafrica.13457.3","DOIUrl":"https://doi.org/10.12688/openresafrica.13457.3","url":null,"abstract":"<ns4:p><ns4:bold>Background:</ns4:bold> Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ) are the essential long-acting partner drugs in the artemisinin-based combination therapies (ACTs) treatment regimens globally. The recent report on the emergence of artemisinin-resistant parasites portends an imminent failure of the partner drug in clearing the high residual parasite densities. Understanding the resistance mechanisms to partner drugs remains critical for tracking resistant parasites. Cysteine desulfurase IscS (<ns4:italic>nfs1</ns4:italic>), one of the proteins involved in the iron-sulfur (FeS) biogenesis pathway, has been implicated in mediating malaria parasite drug resistance. </ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Using the rodent malaria parasites <ns4:italic>Plasmodium berghei </ns4:italic>ANKA in mice, we assessed whether the <ns4:italic>nfs1</ns4:italic> gene is associated with LM, PQ, and AQ resistance. We first verified the stability of the LM, PQ, and AQ-resistant parasites in the standard 4-Day Suppressive Test. By means of PCR and sequencing analysis, we probed for single nucleotide polymorphisms (SNPs) in the <ns4:italic>nfs1</ns4:italic> gene. Using qPCR, we then measured the expression of the <ns4:italic>nfs1 </ns4:italic>gene in resistant parasites relative to the drug-sensitive parent parasites. </ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> Our analyses of <ns4:italic>nfs1</ns4:italic> reveal a non-synonymous Gln142Arg mutation in the LM and PQ-resistant parasites. This mutation was not detected in the AQ-resistant parasites. The mRNA quantification of the <ns4:italic>nfs1</ns4:italic> gene reveals differential expression in both LM and PQ-resistant parasites. Conversely, <ns4:italic>nfs1 </ns4:italic>expression remained unchanged in the AQ-resistant parasites.</ns4:p><ns4:p> <ns4:bold>Conclusion:</ns4:bold> Our data suggest that LM and PQ selection pressure induces nonsynonymous mutation and differential expression of the <ns4:italic>nfs1 </ns4:italic>gene in <ns4:italic>Plasmodium berghei</ns4:italic>. Collectively, these findings provide a premise for investigating LM and PQ resistance mechanisms in both <ns4:italic>P. berghei</ns4:italic> and <ns4:italic>P. falciparum</ns4:italic>.</ns4:p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136299568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Stimulation Therapy for older people with Dementia in Africa: A Scoping Review","authors":"Stephen Ojiambo Wandera, E. Duncan, Monica M. Diaz, D. Ayuku","doi":"10.12688/openresafrica.14092.1","DOIUrl":"https://doi.org/10.12688/openresafrica.14092.1","url":null,"abstract":"Background: Cognitive Stimulation Therapy (CST) is a non-pharmacological intervention developed for dementia that is useful in Africa but has not been studied widely. We reviewed the existing evidence regarding CST among older people living with dementia in Africa. Methods: A systematic literature search on CST among older people with dementia in Africa from 2000-2021 was done in MEDLINE (PubMed), CINAHL (EBSCOhost), and PsycINFO. A narrative approach was taken to chart, synthesize and interpret the data using Microsoft Excel. Results: After removing duplicates using Endnote, a total of 122 studies were retained and screened first by title, then abstract, and finally by full text. Seven articles matched the inclusion/exclusion criteria. CST has been adapted and piloted in two African countries (Nigeria and Tanzania). CST studies in Africa indicate improvements in clinical outcomes including cognition and quality of life. Although there are some barriers to overcome, CST has significant facilitators in an African context. Conclusions: CST is feasible, adaptable, and acceptable in the African countries it has been implemented in. Some cultural barriers, such as religious affiliation and respect for older people, should be overcome. Further research is needed to further evaluate the efficacy of CST in various African contexts.","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42631000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Public engagement by early career researchers in East Africa during the COVID-19 pandemic: case studies from East Africa","authors":"Trizah K. Milugo, Mary V. Mosha, E. Wampande, Rune N Philemon, Immaculate N. Lwanga, J. Seeley, Nelson K Sewankambo","doi":"10.12688/openresafrica.13897.1","DOIUrl":"https://doi.org/10.12688/openresafrica.13897.1","url":null,"abstract":"Background: Community engagement and involvement (CEI) in research usually depends on face-to-face interactions. However, the COVID-19 pandemic prevented such interactions because of national lockdowns and social distancing. This paper highlights the ways in which early career researchers from East Africa tackled CEI activities during the pandemic. Methods: We provide four case examples that illustrate how early-career researchers based in Kenya, Uganda and Tanzania, deployed different approaches and initiatives to community-engaged research during the pandemic to encourage participation and uptake of research findings. Results: All the three early-career researchers attempted to use virtual/digital means to implement the CEI. However, in each country, this attempt was unsuccessful because of poor connectivity, as well as many poorer students lacking access to telephones and computers. Nevertheless, the researchers effectively engaged the students using different activities (making up songs, drawing comics, and taking part in quizzes) once the schools reopened. Conclusion: These results highlight the complexity of implementing community engagement and involvement in health research when face-to-face interaction is not possible. The findings are relevant to researchers who wish to incorporate community engagement in their research and initiatives.","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45028156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lumefantrine pressure selects nonsynonymous mutation in cysteine desulfurase IscS gene in the rodent malaria parasite Plasmodium berghei ANKA","authors":"Beatrice Gachie, Jean Chepngetich, Brenda Muriithi, Kelvin Thiong’o, Jeremiah Gathirwa, Francis Kimani, Peter Mwitari, Gabriel Magoma, Daniel Kiboi","doi":"10.12688/openresafrica.13457.2","DOIUrl":"https://doi.org/10.12688/openresafrica.13457.2","url":null,"abstract":"<ns4:p><ns4:bold>Background:</ns4:bold> Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ) are the essential long-acting partner drugs in the artemisinin-based combination therapies (ACTs) treatment regimens globally. The recent report on the emergence of artemisinin-resistant parasites portends an imminent failure of the partner drug in clearing the high residual parasite densities. Understanding the resistance mechanisms to partner drugs remains critical for tracking resistant parasites. Cysteine desulfurase IscS (<ns4:italic>nfs1</ns4:italic>), one of the proteins involved in the iron-sulfur (FeS) biogenesis pathway, has been implicated in mediating malaria parasite drug resistance. </ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Using the rodent malaria parasites <ns4:italic>Plasmodium berghei </ns4:italic>ANKA in mice, we assessed whether the <ns4:italic>nfs1</ns4:italic> gene is associated with LM, PQ, and AQ resistance. We first verified the stability of the LM, PQ, and AQ-resistant parasites in the standard 4-Day Suppressive Test. By means of PCR and sequencing analysis, we probed for single nucleotide polymorphisms (SNPs) in the <ns4:italic>nfs1</ns4:italic> gene. Using qPCR, we then measured the expression of the nfs1 gene in resistant parasites relative to the drug-sensitive parent parasites. </ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> Our analyses of nfs1 reveal a non-synonymous Gln142Arg mutation in the LM and PQ-resistant parasites. This mutation was not detected in the AQ-resistant parasites. The mRNA quantification of the <ns4:italic>nfs1</ns4:italic> gene reveals differential expression in both LM and PQ-resistant parasites. Conversely, nfs1 expression remained unchanged in the AQ-resistant parasites.</ns4:p><ns4:p> <ns4:bold>Conclusion:</ns4:bold> Our data suggest that LM and PQ selection pressure induces nonsynonymous mutation and differential expression of the nfs1 gene in <ns4:italic>Plasmodium berghei</ns4:italic>. Collectively, these findings provide a premise for investigating LM and PQ resistance mechanisms in both <ns4:italic>P. berghei</ns4:italic> and <ns4:italic>P. falciparum</ns4:italic>.</ns4:p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"144 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136340126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in Plasmodium berghei ANKA","authors":"Jean Chepngetich, Brenda Muriithi, Beatrice Gachie, Kevin Thiong'o, Mercy Jepkorir, Jeremiah Gathirwa, Francis Kimani, Peter Mwitari, Daniel Kiboi","doi":"10.12688/openresafrica.13436.2","DOIUrl":"https://doi.org/10.12688/openresafrica.13436.2","url":null,"abstract":"<ns4:p><ns4:bold>Background:</ns4:bold> Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable <ns4:italic>Plasmodium</ns4:italic> kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant <ns4:italic>Plasmodium berghei</ns4:italic> parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kβ), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in <ns4:italic>Plasmodium berghei</ns4:italic> ANKA.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> We used <ns4:italic>in</ns4:italic> <ns4:italic>silico</ns4:italic> bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1. Using qPCR analysis, we finally measured the mRNA amount of PANK1, DAGK, and PI4Kβ at trophozoites and schizonts stages.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kβ possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His, while DAGK contained K270R and K292R mutations. PI4Kβ had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kβ in the trophozoites but upregulation at the schizonts stages in the AQr parasites.</ns4:p><ns4:p> <ns4:bold>Conclusions:</ns4:bold> The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and the impact on drug responses require further investigations in malaria parasites.</ns4:p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"140 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136335316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interconnected global emergencies of climate change, food security and health: a call to action by the Science for Africa Foundation.","authors":"Thomas Kariuki, Judith Omumbo, Kabura Ciugu, Elizabeth Marincola","doi":"10.12688/openresafrica.13566.1","DOIUrl":"10.12688/openresafrica.13566.1","url":null,"abstract":"<p><p>The evidence is clear that climate change is the greatest challenge facing mankind today. Africa is disproportionately burdened by multiple direct and cascading impacts of the climate crisis. Global investments for climate change adaptation, however, have not prioritized Africa adequately and there is a significant knowledge gap in understanding the context and science of climate change and sustainable solutions for the continent's adaptation. Solutions for adaptation and resilience are made complex by an urgent need for accelerated economic growth, rapid population expansion and urbanization, habitat and biodiversity loss and dwindling financing.  There are also challenges in matching policies, wavering commitments and actions with good science that focuses on sustainable lives, livelihoods and ecosystem preservation. The solutions must come from where the impacts are felt. The Science for Africa Foundation supports African researchers and institutions to lead in the science that addresses African priority development areas and has set climate change as a strategic priority. This call to action, by the SFA Foundation, outlines key areas that its strategy addresses through programs that support African scientific excellence, leadership and the best of Africa's research to understand the science of climate change and its impacts; collate and assess evidence for policy; grow high level technical capacity on the continent; and create innovative priority actions for Africa.</p>","PeriodicalId":74358,"journal":{"name":"Open research Africa","volume":"6 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2023-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10794259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}